The influence of carrier and drug morphology on drug delivery from dry powder formulations

Larhrib, Hassan; Martin, Gary P.; Marriott, Christopher; Prime, David

doi:10.1016/s0378-5173(03)00156-x

Cited by 153 publications

(77 citation statements)

References 11 publications

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“…10,37) Based on the strategy of increasing FPF by decreasing the drug-carrier interaction, various techniques have been studied in order to improve the inhalation properties of DPI. 22,[38][39][40][41][42] A schematic diagram of the estimated relation between the drug-carrier interaction and the inhalation properties is illustrated in Fig. 8.…”

Section: Discussionmentioning

confidence: 99%

Application and Mechanism of Inhalation Profile Improvement of DPI Formulations by Mechanofusion with Magnesium Stearate

et al. 2008

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Dry powder inhaler (DPI) formulations have been utilized in the treatment of respiratory disease [1][2][3] and for systemic administration.4 -7) They have become common in the inhalation therapy field because of various advantages, such as being free from anti-environmental propellants 8) and ease of use with portable small devices.DPI formulations with fine drug particles and coarse carrier particles have been widely used for a long time. Usually their components are simple and they can be manufactured with conventional equipment. Therefore, they appear to be a valuable option as the formulation for clinical trials, especially in the early stages of development. The carrier particles play the critical role in preventing the agglomeration of fine drug particles which possesses high surface energy due to their large specific surface area. On the other hand, it is necessary to achieve the high deposition in the deep lungs to satisfy the required bioavailability. Because only small particles (aerodynamic diameter below 5 mm) can reach the lungs, fine drug particles should be detached from the coarse carrier particles through the inhalation process. The percentage of small particles to the entire dose is defined as fine particle fraction (FPF). Therefore, FPF is an index of the extent of deposition in the lungs.Studies have been conducted to clarify the factors that control the inhalation properties of the carrier-based DPI formulations. [9][10][11][12][13][14] Many studies focused on the carrier surface properties especially rugosity and/or coverage of high energy binding sites. 10,[15][16][17][18][19][20][21] Surface energy of particles would be one of the major factors influencing the inhalation profile of DPI including FPF. 22,23) However the mechanism of FPF increase has not been fully clarified so far. This seems to be because the inhalation profile of DPI is affected by various factors including particle size, morphology electrostatic charge and inhalation condition. 10,12,[24][25][26] Therefore, there is a need for preparation and characterization of series of powder samples that are different in surface properties but similar in other properties and compare them under the same inhalation condition.Mechanofusion can modify the surface energy of lactose carrier particles without drastic change of the particle size and can make the particle shape round to lessen the differences.Inverse gas chromatography (IGC) has been utilized to examine the effect of surface energy on the inhalation behavior of DPI. We reported that mechanofusion on a lactose carrier changed the carrier's surface condition and the inhalation properties of DPI formulations containing the lactose carrier and Compound A.27) The Andersen cascade impactor (ACI) profile suggested that the increase of FPF was accompanied by the decrease of the interaction between Compound A and carrier particles. Begat et al. also reported that mechanofusion of lactose with Mg-St reduced the interaction between drug and lactose particles.28) Mg-St is known as lubri...

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Section: Discussionmentioning

confidence: 99%

Application and Mechanism of Inhalation Profile Improvement of DPI Formulations by Mechanofusion with Magnesium Stearate

et al. 2008

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“…The characterization of particle flowability using CI is based on empirical understanding and may pose discrepancies in result interpretation. Therefore, flowability demonstration was also conducted by θ (27).…”

Section: Powder Flowabilitymentioning

confidence: 99%

Effect of Particle Shape on Dry Particle Inhalation: Study of Flowability, Aerosolization, and Deposition Properties

2009

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Abstract. The shape effects of dry particles on flowability, aerosolization, and deposition properties in inhalation drug delivery are studied. The properties are compared with similar size range particles of different shapes such as sphere, needle, cube, plate, and pollen. Flowability of the particles is characterized by Carr's compressibility index and angle of slide (θ) method. The aerosolization and deposition properties of the particles are studied in vitro using an eight-stage Anderson cascade impactor with a Rotahaler®. Pollen-shaped particles are found to exhibit better flowability, higher emitted dose, and higher fine particle fraction than particles of other shapes in similar size range. They showed minimum θ of 35°and maximum emitted dose of 87% and fine particle fraction of 16%. The use of pollen-shaped particles can be a potential improvement in dry particle inhalation.

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“…A surface treatment approach, based on interplay at the solidliquid interface in a drug suspension, was successfully applied on APIs with poor flowability (14,15). The recrystallization of sulfadiazine, methyldopa, and salbutamol sulfate from preselected solvents in the absence or presence of additive has been carried out to change crystal habit with altering surface topography (14,16).…”

Section: Introductionmentioning

confidence: 99%

Effective Modification of Particle Surface Properties Using Ultrasonic Water Mist

et al. 2009

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Abstract. The goal of the present study was to design a new technique to modify particle surface properties and, through that, to improve flowability of poorly flowing drug thiamine hydrochloride and pharmaceutical sugar lactose monohydrate of two different grades. The powdered particles were supplied by a vibratory feeder and exposed to an instantaneous effect of water mist generated from an ultrasound nebulizer. The processed and original powders were evaluated with respect to morphology (scanning electron microscopy, atomic force microscopy, and spatial filtering technique), flow, and solid state properties. It was found that rapid exposition of pharmaceutical materials by water mist resulted in the improvement of powder technical properties. The evident changes in flowability of coarser lactose were obviously due to smoothing of particle surface and decreasing in the level of fines with very slight increment in particle size. The changes in thiamine powder flow were mainly due to narrowing in particle size distribution where the tendency for better flow of finer lactose was related to surface and size modifications. The aqueous mist application did not cause any alteration of the crystal structures of the studied materials. The proposed water mist treatment technique appears to be a robust, rapid, and promising tool for the improvement of the technological properties of pharmaceutical powders.

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The influence of carrier and drug morphology on drug delivery from dry powder formulations

Cited by 153 publications

References 11 publications

Application and Mechanism of Inhalation Profile Improvement of DPI Formulations by Mechanofusion with Magnesium Stearate

Application and Mechanism of Inhalation Profile Improvement of DPI Formulations by Mechanofusion with Magnesium Stearate

Effect of Particle Shape on Dry Particle Inhalation: Study of Flowability, Aerosolization, and Deposition Properties

Effective Modification of Particle Surface Properties Using Ultrasonic Water Mist

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